p23_like domain similar to the C-terminal (tail) domain of vertebrate Melusin and related proteins. Melusin's tail domain interacts with the cytoplasmic domain of beta1-A and beta1-D isoforms of beta1 integrin, it does not bind other integrin beta subunits. Melusin is a muscle-specific protein expressed in skeletal and cardiac muscles but not in smooth muscle or other tissues. It is needed for heart hypertrophy following mechanical overload. The integrin-binding portion of this domain appears to be sequestered in the full length melusin protein, Ca2+ may modulate the protein's conformation exposing this binding site. This group includes Chordc1, also known as Chp-1, which is conserved from vertebrates to humans. Mammalian Chordc1 interacts with the heat shock protein (HSP) Hsp90 and is implicated in circadian and/or homeostatic mechanisms in the brain. The N-terminal portions of proteins belonging to this group contain two cysteine and histidine rich domain (CHORD) domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 231 CRFDWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEP 310
Cdd:cd06488   1 CRHDWHQTGSHVVVSVYAKNSNPELSVVEANSTVLTIHIVFEGNKEFQLDIELWGVIDVEKSSVNMLPTKVEIKLRKAEP 80

                ....*..
gi 68448475 311 MSWARLD 317
Cdd:cd06488  81 GSWAKLE 87

CHORD; CHORD represents a Zn binding domain. Silencing of the C. elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 68448475   157 TACKNGGCMKTYNGPKTDEEMCLYHSGVPIFHEGMKYWSCCKRKTSDFNTFLSQEGCNKGSH 218
Cdd:pfam04968   1 TKCKNKGCGKTFDEEENNDDACTYHPGAPIFHEGSKGWSCCKKRVLDFDEFLKIPGCTTGKH 62

p23_like domain similar to the C-terminal (tail) domain of vertebrate Melusin and related proteins. Melusin's tail domain interacts with the cytoplasmic domain of beta1-A and beta1-D isoforms of beta1 integrin, it does not bind other integrin beta subunits. Melusin is a muscle-specific protein expressed in skeletal and cardiac muscles but not in smooth muscle or other tissues. It is needed for heart hypertrophy following mechanical overload. The integrin-binding portion of this domain appears to be sequestered in the full length melusin protein, Ca2+ may modulate the protein's conformation exposing this binding site. This group includes Chordc1, also known as Chp-1, which is conserved from vertebrates to humans. Mammalian Chordc1 interacts with the heat shock protein (HSP) Hsp90 and is implicated in circadian and/or homeostatic mechanisms in the brain. The N-terminal portions of proteins belonging to this group contain two cysteine and histidine rich domain (CHORD) domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 231 CRFDWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEP 310
Cdd:cd06488   1 CRHDWHQTGSHVVVSVYAKNSNPELSVVEANSTVLTIHIVFEGNKEFQLDIELWGVIDVEKSSVNMLPTKVEIKLRKAEP 80

                ....*..
gi 68448475 311 MSWARLD 317
Cdd:cd06488  81 GSWAKLE 87

CHORD; CHORD represents a Zn binding domain. Silencing of the C. elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 68448475   157 TACKNGGCMKTYNGPKTDEEMCLYHSGVPIFHEGMKYWSCCKRKTSDFNTFLSQEGCNKGSH 218
Cdd:pfam04968   1 TKCKNKGCGKTFDEEENNDDACTYHPGAPIFHEGSKGWSCCKKRVLDFDEFLKIPGCTTGKH 62

SGT1, suppressor of G2 allele of SKP1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475  232 RFDWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEPM 311
Cdd:PLN03088 158 RHEFYQKPEEVVVTVFAKGVPAENVNVDFGEQILSVVIEVPGEDAYHLQPRLFGKIIPDKCKYEVLSTKIEIRLAKAEPI 237

                 ....*.
gi 68448475  312 SWARLD 317
Cdd:PLN03088 238 TWASLE 243

p23_like domain similar to the C-terminal (tail) domain of vertebrate Melusin and related proteins. Melusin's tail domain interacts with the cytoplasmic domain of beta1-A and beta1-D isoforms of beta1 integrin, it does not bind other integrin beta subunits. Melusin is a muscle-specific protein expressed in skeletal and cardiac muscles but not in smooth muscle or other tissues. It is needed for heart hypertrophy following mechanical overload. The integrin-binding portion of this domain appears to be sequestered in the full length melusin protein, Ca2+ may modulate the protein's conformation exposing this binding site. This group includes Chordc1, also known as Chp-1, which is conserved from vertebrates to humans. Mammalian Chordc1 interacts with the heat shock protein (HSP) Hsp90 and is implicated in circadian and/or homeostatic mechanisms in the brain. The N-terminal portions of proteins belonging to this group contain two cysteine and histidine rich domain (CHORD) domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 231 CRFDWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEP 310
Cdd:cd06488   1 CRHDWHQTGSHVVVSVYAKNSNPELSVVEANSTVLTIHIVFEGNKEFQLDIELWGVIDVEKSSVNMLPTKVEIKLRKAEP 80

                ....*..
gi 68448475 311 MSWARLD 317
Cdd:cd06488  81 GSWAKLE 87

p23_like domain similar to the C-terminal CHORD-SGT1 (CS) domain of Sgt1 (suppressor of G2 allele of Skp1). Sgt1 interacts with multiple protein complexes and has the features of a cochaperone. Human (h) Sgt1 interacts with both Hsp70 and Hsp90, and has been shown to bind Hsp90 through its CS domain. Saccharomyces cerevisiae (Sc) Sgt1 is a subunit of both core kinetochore and SCF (Skp1-Cul1-F-box) ubiquitin ligase complexes. Sgt1 is required for pathogen resistance in plants. ScSgt1 is needed for the G1/S and G2/M cell-cycle transitions, and for assembly of the core kinetochore complex (CBF3) via activation of Ctf13, the F-box protein. Binding of Hsp82 (a yeast Hsp90 homologue) to ScSgt1, promotes the binding of Sgt1 to Skp1 and of Skp1 to Ctf13. Some proteins in this group have an SGT1-specific (SGS) domain at the extreme C-terminus. The ScSgt1-SGS domain binds adenylate cyclase. The hSgt1-SGS domain interacts with some S100 family proteins, and studies suggest that the interaction of hSgt1 with Hsp90 and Hsp70 may be regulated by S100A6 in a Ca2+ dependent fashion. This group also includes the p23_like domains of Melusin and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR). Melusin is a vertebrate protein which interacts with two splice variants of beta1 integrin, and NCB5OR plays a part in maintaining viable pancreatic beta cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 234 DWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEPMSW 313
Cdd:cd06466   1 DWYQTDTSVTVTIYAKNVDKEDVKVEFNEQSLSVSIILPGGSEYQLELDLFGPIDPEQSKVSVLPTKVEITLKKAEPGSW 80

                ....
gi 68448475 314 ARLD 317
Cdd:cd06466  81 PSLE 84

Proteins containing this p23_like domain include p23 and its Saccharomyces cerevisiae (Sc) homolog Sba1. Both are co-chaperones for the heat shock protein (Hsp) 90. p23 binds Hsp90 and participates in the folding of a number of Hsp90 clients, including the progesterone receptor. p23 also has a passive chaperoning activity and in addition may participate in prostaglandin synthesis. Both p23 and Sba1p can regulate telomerase activity. This group includes domains similar to the C-terminal CHORD-SGT1 (CS) domain of suppressor of G2 allele of Skp1 (Sgt1). Sgt1 interacts with multiple protein complexes and has the features of a co-chaperone. Human (h) Sgt1 interacts with both Hsp70 and Hsp90, and has been shown to bind Hsp90 through its CS domain. Saccharomyces cerevisiae (Sc) Sgt1 is a subunit of both core kinetochore and SCF (Skp1-Cul1-F-box) ubiquitin ligase complexes. Sgt1 is required for pathogen resistance in plants. This group also includes the p23_like domains of human butyrate-induced transcript 1 (hB-ind1), NUD (nuclear distribution) C, Melusin, and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR). hB-ind1 plays a role in the signaling pathway mediated by the small GTPase Rac1, NUDC is needed for nuclear movement, Melusin interacts with two splice variants of beta1 integrin, and NCB5OR plays a part in maintaining viable pancreatic beta cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 235 WHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEPM-SW 313
Cdd:cd06463   1 WYQTLDEVTITIPLKDVTKKDVKVEFTPKSLTVSVKGGGGKEYLLEGELFGPIDPEESKWTVEDRKIEITLKKKEPGeWW 80

                ...
gi 68448475 314 ARL 316
Cdd:cd06463  81 PRL 83

p23_like domain similar to the C-terminal CS (CHORD-SGT1) domain of human (h) Sgt1 and related proteins. hSgt1 is a co-chaperone which has been shown to be elevated in HEp-2 cells as a result of stress conditions such as heat shock. It interacts with the heat shock proteins (HSPs) Hsp70 and Hsp90, and it expression pattern is synchronized with these two Hsps. The interaction with HSP90 has been shown to involve the hSgt1_CS domain, and appears to be required for correct kinetochore assembly and efficient cell division. Some proteins in this subgroup contain a tetratricopeptide repeat (TPR) HSP-binding domain N-terminal to this CS domain, and most proteins in this subgroup contain a Sgt1-specific (SGS) domain C-terminal to the CS domain. The SGS domain interacts with some S100 family proteins. Studies suggest that S100A6 modulates in a Ca2+ dependent manner the interactions of hSgt1 with Hsp90 and Hsp70. The yeast Sgt1 CS domain is not found in this subgroup.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 234 DWHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGEKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEPMSW 313
Cdd:cd06489   1 DWYQTESQVVITILIKNVKPEDVSVEFEKRELSATVKLPSGNDYSLKLHLLHPIVPEQSSYKILSTKIEIKLKKTEAIRW 80

                ....
gi 68448475 314 ARLD 317
Cdd:cd06489  81 SKLE 84

This domain family includes the alpha-crystallin domain (ACD) of alpha-crystallin-type small heat shock proteins (sHsps) and a similar domain found in p23-like proteins. sHsps are small stress induced proteins with monomeric masses between 12 -43 kDa, whose common feature is this ACD. sHsps are generally active as large oligomers consisting of multiple subunits, and are believed to be ATP-independent chaperones that prevent aggregation and are important in refolding in combination with other Hsps. p23 is a cochaperone of the Hsp90 chaperoning pathway. It binds Hsp90 and participates in the folding of a number of Hsp90 clients including the progesterone receptor. p23 also has a passive chaperoning activity. p23 in addition may act as the cytosolic prostaglandin E2 synthase. Included in this family is the p23-like C-terminal CHORD-SGT1 (CS) domain of suppressor of G2 allele of Skp1 (Sgt1) and the p23-like domains of human butyrate-induced transcript 1 (hB-ind1), NUD (nuclear distribution) C, Melusin, and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68448475 235 WHQTGSQVTLSIYAKNSNPQLCSVEANSVSLKVHLIFEGE-------KEFELSLSLWGVIDVSKSVVNMMASKVEVVMKK 307
Cdd:cd00298   1 WYQTDDEVVVTVDLPGVKKEDIKVEVEDNVLTISGKREEEeerersyGEFERSFELPEDVDPEKSKASLENGVLEITLPK 80

p23_like domain found in human (h) butyrate-induced transcript 1 (B-ind1) and similar proteins. hB-ind1 participates in signaling by the small GTPase Rac1. It binds to Rac1 and enhances different Rac1 effects including activation of nuclear factor (NF) kappaB and activation of c-Jun N-terminal kinase (JNK). hB-ind1 also plays a part in the RNA replication and particle production of Hepatitis C virus (HCV) through its interaction with heat shock protein Hsp90, HCV nonstructural protein 5A (NS5A), and the immunophilin FKBP8. hB-ind1 is upregulated in the outer layer of Chinese hamster V79 cells grown as multicell spheroids, versus in the same cells grown as monolayers. This group includes the Saccharomyces cerevisiae Sba1, a co-chaperone of the Hsp90. Sba1 has been shown to be is required for telomere length maintenance, and may modulate telomerase DNA-binding activity.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 68448475 268 HLIFEG-----EKEFELSLSLWGVIDVSKSVVNMMASKVEVVMKKAEPMS-WARL 316
Cdd:cd06465  32 SLSFKAkggggGKKYEFDLEFYKEIDPEESKYKVTGRQIEFVLRKKEAGEyWPRL 86